Alzheimer's disease (AD) is one of the most common and debilitating neurodegenerative diseases of older Americans. Several treatments show promise in slowing the development of AD, but to be truly effective, they must be started before full-blown AD appears. The prodromal phase of AD produces symptoms of mild cognitive impairment (MCI), but an ideal test would detect signs of incipient AD even before the appearance of MCI. The goal of this project is to develop a test that can detect changes in brain proteins that are associated with AD by measuring their levels in blood. Since the levels of these proteins such as tau and bAP are very low in blood, a very sensitive test is needed. BioTraces has developed two immunoassays, IA/MPD and Super-ELISA that have the requisite sensitivity. However, even though these assays can measure tau and bAP in the blood, the total levels in blood might reflect the integrity of the blood-brain barrier as much as the absolute brain levels. Thus, a test to measure the ratio of phosphorylated to total tau in blood is also proposed since this ratio appears to increase the specificity even of CSF-based tests and the ratio should be much less sensitive to variations in the blood-brain barrier. After developing the assays to tau and bAP to the required sensitivity, they will be validated as AD tests by measuring and comparing blood samples from people with and without AD or MCI.